Modifications in Perfringolysin O Domain 4 Alter the Cholesterol Concentration Threshold Required for Binding.
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| Title: | Modifications in Perfringolysin O Domain 4 Alter the Cholesterol Concentration Threshold Required for Binding. |
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| Authors: | Johnson, Benjamin B.1, Moe, Paul C.2, Wang, David3, Rossi, Kathleen3, Trigatti, Bernardo L.3, Heuck, Alejandro P.1,2 heuck@biochem.umass.edu |
| Source: | Biochemistry. 4/24/2012, Vol. 51 Issue 16, p3373-3382. 10p. |
| Subjects: | Cell analysis, Cell membrane chemistry, Physiological effects of cholesterol, Arterial abnormalities, Sterol regulatory element-binding proteins, Clostridium perfringens, Bilayer lipid membranes |
| Abstract: | Changes in the cholesterol content of cell membranes affect many physiological and pathological events, including the formation of arterial plaques, the entry of virus into cells, and receptor organization. Measuring the trafficking and distribution of cholesterol is essential to understanding how cells regulate sterol levels in membranes. Perfringolysin O (PFO) is a cytolysin secreted by Clostridium perfringens that requires cholesterol in the target membrane for binding. The specificity of PFO for high levels of cholesterol makes the toxin an attractive tool for studying the distribution and trafficking of cholesterol in cells. However, the use of the native toxin is limited given that binding is triggered only above a determined cholesterol concentration. To this end, we have identified mutations in PFO that altered the threshold for how much cholesterol is required to trigger binding. The cholesterol threshold among different PFO derivatives varied up to 10 mol % sterol, and these variations were not dependent on the lipid composition of the membrane. We characterized the binding of these PFO derivatives on murine macrophage-like cells whose cholesterol content was reduced or augmented. Our findings revealed that engineered PFO derivatives differentially associated with these cells in response to changes in cholesterol levels in the plasma membrane. [ABSTRACT FROM AUTHOR] |
| Copyright of Biochemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 86162223 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Modifications in Perfringolysin O Domain 4 Alter the Cholesterol Concentration Threshold Required for Binding. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Johnson%2C+Benjamin+B%2E%22">Johnson, Benjamin B.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Moe%2C+Paul+C%2E%22">Moe, Paul C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Wang%2C+David%22">Wang, David</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Rossi%2C+Kathleen%22">Rossi, Kathleen</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Trigatti%2C+Bernardo+L%2E%22">Trigatti, Bernardo L.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Heuck%2C+Alejandro+P%2E%22">Heuck, Alejandro P.</searchLink><relatesTo>1,2</relatesTo><i> heuck@biochem.umass.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Biochemistry%22">Biochemistry</searchLink>. 4/24/2012, Vol. 51 Issue 16, p3373-3382. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cell+analysis%22">Cell analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+membrane+chemistry%22">Cell membrane chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Physiological+effects+of+cholesterol%22">Physiological effects of cholesterol</searchLink><br /><searchLink fieldCode="DE" term="%22Arterial+abnormalities%22">Arterial abnormalities</searchLink><br /><searchLink fieldCode="DE" term="%22Sterol+regulatory+element-binding+proteins%22">Sterol regulatory element-binding proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Clostridium+perfringens%22">Clostridium perfringens</searchLink><br /><searchLink fieldCode="DE" term="%22Bilayer+lipid+membranes%22">Bilayer lipid membranes</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Changes in the cholesterol content of cell membranes affect many physiological and pathological events, including the formation of arterial plaques, the entry of virus into cells, and receptor organization. Measuring the trafficking and distribution of cholesterol is essential to understanding how cells regulate sterol levels in membranes. Perfringolysin O (PFO) is a cytolysin secreted by Clostridium perfringens that requires cholesterol in the target membrane for binding. The specificity of PFO for high levels of cholesterol makes the toxin an attractive tool for studying the distribution and trafficking of cholesterol in cells. However, the use of the native toxin is limited given that binding is triggered only above a determined cholesterol concentration. To this end, we have identified mutations in PFO that altered the threshold for how much cholesterol is required to trigger binding. The cholesterol threshold among different PFO derivatives varied up to 10 mol % sterol, and these variations were not dependent on the lipid composition of the membrane. We characterized the binding of these PFO derivatives on murine macrophage-like cells whose cholesterol content was reduced or augmented. Our findings revealed that engineered PFO derivatives differentially associated with these cells in response to changes in cholesterol levels in the plasma membrane. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Biochemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1021/bi3003132 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 3373 Subjects: – SubjectFull: Cell analysis Type: general – SubjectFull: Cell membrane chemistry Type: general – SubjectFull: Physiological effects of cholesterol Type: general – SubjectFull: Arterial abnormalities Type: general – SubjectFull: Sterol regulatory element-binding proteins Type: general – SubjectFull: Clostridium perfringens Type: general – SubjectFull: Bilayer lipid membranes Type: general Titles: – TitleFull: Modifications in Perfringolysin O Domain 4 Alter the Cholesterol Concentration Threshold Required for Binding. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Johnson, Benjamin B. – PersonEntity: Name: NameFull: Moe, Paul C. – PersonEntity: Name: NameFull: Wang, David – PersonEntity: Name: NameFull: Rossi, Kathleen – PersonEntity: Name: NameFull: Trigatti, Bernardo L. – PersonEntity: Name: NameFull: Heuck, Alejandro P. IsPartOfRelationships: – BibEntity: Dates: – D: 24 M: 04 Text: 4/24/2012 Type: published Y: 2012 Identifiers: – Type: issn-print Value: 00062960 Numbering: – Type: volume Value: 51 – Type: issue Value: 16 Titles: – TitleFull: Biochemistry Type: main |
| ResultId | 1 |
